Spatial learning by rats across visually disconnected environments

Experiments were designed to examine some properties of spatial representations in rats. Adult subjects were trained to escape through a hole at a fixed position in a large circular arena (see Schenk 1989). The experiments were conducted in the dark, with a limited number of controlled visual light cues in order to assess the minimal cue requirement for place learning. Three identical light cues (shape, height and distance from the table) were used. Depending on the condition, they were either permanently on, or alternatively on or off, depending on the position of the rat in the field. Two questions were asked: a) how many identical visual cues were necessary for spatial discrimination in the dark, and b) could rats integrate the relative positions of separate cues, under conditions in which the rat was never allowed to perceive all three cues simultaneously. The results suggest that rats are able to achieve a place discrimination task even if the three cues necessary for efficient orientation can never be seen simultaneously. A dissociation between the discrimination of the spatial position of the goal and the capacity to reach it by a direct path suggests that a reduced number of cues might require prolonged locomotion to allow an accurate orientation in the environment.

Antiviral therapy against chronic hepatitis B in Brazil: high rates of lamivudine resistance mutations and correlation with HBV genotypes

The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).

Biotic factors and occurrence of Lutzomyia longipalpis in endemic area of visceral leishmaniasis, Mato Grosso do Sul, Brazil

The relationships between environmental exposure to risk agents and health conditions have been studied with the aid of remote sensing imagery, a tool particularly useful in the study of vegetation cover. This study aims to evaluate the influence of environmental variables on the spatial distribution of the abundance of Lutzomyia longipalpis and the reported canine and human visceral leishmaniasis (VL) cases at an urban area of Campo Grande, state of Mato Grosso do Sul. The sandfly captures were performed in 13 residences that were selected by raffle considering four residences or collection station for buffer. These buffers were generated from the central house with about 50, 100 and 200 m from it in an endemic area of VL. The abundance of sandflies and human and canine cases were georreferenced using the GIS software PCI Geomatica. The normalized difference vegetation index (NDVI) and percentage of land covered by vegetation were the environmental variables extracted from a remote sensing IKONOS-2 image. The average NDVI was considered as the complexity of habitat and the standard deviation as the heterogeneity of habitat. One thousand three hundred sixty-seven specimens were collected during the catch. We found a significant positive linear correlation between the abundance of sandflies and the percentage of vegetation cover and average NDVI. However, there was no significant association between habitat heterogeneity and the abundance of these flies.

Genotype-phenotype correlation of age-related macular degeneration : influence of complement factor H polymorphism

RAPPORT DE SYNTHESE La dégénérescence maculaire liée à l'âge (DMLA) est une maladie très fréquente qui représente la cause principale de cécité légale chez les sujets de plus de 50 ans en Occident. Bien que l'étiologie exacte de cette affection ne soit pas complètement connue, des facteurs environnementaux et génétiques influencent sa survenue et son évolution. A ce sujet, de récentes recherches ont notamment montré une association marquée à une variante du gène CFH, Y402H. Nous ignorons toutefois si le polymorphisme Y402H est associé à un phénotype particulier de la maladie. Cette étude a pour but d'établir si cette variante du gène CFH est associée à certaines caractéristiques phénotypiques précoces. L'étude porte sur quatre cent vingt patients atteints de DMLA qui ont été phénotypés sur la base de photographie du fond d'oeil (International Classification and Grading system for age- related macular degeneration) et génotypés à partir d'ADN leucocytaire à la recherche de la variante Y402H du gène CFH. Ces données ont ensuite fait l'objet d'une analyse statistique de l'association génotype-phénotype (le génotype de 50 sujets-contrôle a été utilisé pour confirmer l'association du polymorphisme avec la DMLA). Les résultats obtenus, corrigés pour l'âge et le sexe, montrent un odds ratio (OR) de développer une DMLA de 2.95 en présence d'au moins un allèle à risque C et de 9.05 pour les homozygotes CC. Par contre, aucune influence n'est observée sur les stades de la maladie (précoce-tardif)? Une association significative entre le génotype CC et la présence de druses périphériques (p=0.028), ainsi que la localisation centrale des druses (p=0,049) a été mise en évidence. Aucune autre tendance n'a été dégagée concernant les critères restants (taille, surface totale recouverte, localisation nasale des druses) ou les changements pigmentaires. Cette étude a permis de confirmer l'association entre la variante Y4G2H et la DMLA dans la population suisse et de conclure que la variante Y402H du gène CFH présente une association géno-phénotypique pour certaines caractéristiques des druses. Il est probable que d'autres facteurs génétiques encore influencent le phénotype de la DMLA. De nouvelles recherches seront nécessaires pour préciser l'influence de ces autres facteurs génétiques ou environnementaux, en vue d'une meilleure compréhension de la pathogenèse de cette affection, et pour développer des mesures thérapeutiques et prophylactiques adaptées.

Lutzomyia longipalpis abundance in the city of Posadas, northeastern Argentina: variations at different spatial scales

The distribution of Lutzomyia longipalpis is heterogeneous with a pattern of high abundance areas (HAAs) embedded in a matrix of low abundance areas (LAAs). The objective of this study was to describe the variability in the abundance of Lu. longipalpis at two different spatial levels and to analyse the relationship between the abundance and multiple environmental variables. Of the environmental variables analysed in each household, the condition that best explained the differences in vector abundance between HAA-LAA was the variable "land_grass", with greater average values in the peridomestic environments within the LAA, and the variables "#sp tree", "#pots" and "dist_water" that were higher in the HAA. Of the environmental variables analysed in the patches, the variable "unpaved_streets" was higher in the LAAs and the variable "prop_inf_dogs" was higher in the HAAs. An understanding of the main environmental variables that influence the vector distribution could contribute to the development of strategies for the prevention and control of visceral leishmaniasis (VL). This is the first work in which environmental variables are analysed at the micro-scale in urban areas at the southern edge of the current range of Lu. longipalpis. Our results represent a significant contribution to the understanding of the abundance of the vector in the peridomestic habitats of the region.

Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT.

Detection of replication-defective hepatitis A virus based on the correlation between real-time polymerase chain reaction and ELISA in situ results

ELISA in situ can be used to titrate hepatitis A virus (HAV) particles and real-time polymerase chain reaction (RT-PCR) has been shown to be a fast method to quantify the HAV genome. Precise quantification of viral concentration is necessary to distinguish between infectious and non-infectious particles. The purpose of this study was to compare cell culture and RT-PCR quantification results and determine whether HAV genome quantification can be correlated with infectivity. For this purpose, three stocks of undiluted, five-fold diluted and 10-fold diluted HAV were prepared to inoculate cells in a 96-well plate. Monolayers were then incubated for seven, 10 and 14 days and the correlation between the ELISA in situ and RT-PCR results was evaluated. At 10 days post-incubation, the highest viral load was observed in all stocks of HAV via RT-PCR (10(5) copies/mL) (p = 0.0002), while ELISA revealed the highest quantity of particles after 14 days (optical density = 0.24, p < 0.001). At seven days post-infection, there was a significant statistical correlation between the results of the two methods, indicating equivalents titres of particles and HAV genome during this period of infection. The results reported here indicate that the duration of growth of HAV in cell culture must be taken into account to correlate genome quantification with infectivity.

Correlation between plasma concentration of cilazapril and haemodynamic and hormonal effects in healthy man.

1. The haemodynamic and humoral effects of cilazapril, a new angiotensin converting enzyme (ACE) inhibitor, were evaluated in normotensive healthy volunteers. 2. Single oral doses of 1.25, 2.5, 5 and 10 mg of cilazapril inhibited ACE by greater than or equal to 90% and induced the expected pattern of changes of the renin-angiotensin-aldosterone-system. 3. Cilazapril had a long duration of action, since some ACE inhibition was still present 72 h after drug intake. 4. Cilazapril administered intravenously at doses of 5 and 20 micrograms kg-1 for 24 h did not produce any significant effects. 5. During repeated administration of cilazapril for 8 days, no accumulation of cilazaprilat was observed and the clinical tolerance was excellent. 6. In normal volunteers, cilazapril administered orally acts as a potent inhibitor of converting enzyme.

Spatial and temporal changes in Lutzomyia longipalpis abundance, a Leishmania infantum vector in an urban area in northeastern Argentina

This study aimed to analyse changes in the spatial distribution of Lutzomyia longipalpis in Posadas, an urban area located in northeastern Argentina. Data were obtained during the summer of 2007 and 2009 through two entomological surveys of peridomiciles distributed around the city. The abundance distribution pattern for 2009 was computed and compared with the previous pattern obtained in 2007, when the first human visceral leishmaniasis cases were reported in the city. Vector abundance was also examined in relation to micro and macrohabitat characteristics. In 2007 and 2009, Lu. longipalpis was distributed among 41.5% and 31% of the households in the study area, respectively. In both years, the abundance rates at most of the trapping sites were below 30 Lu. longipalpis per trap per night; however, for areas exhibiting 30-60 Lu. longipalpis and more than 60 Lu. longipalpis, the areas increased in both size and number from 2007-2009. Lu. longipalpis was more abundant in areas with a higher tree and bush cover (a macrohabitat characteristic) and in peridomiciles with accumulated unused material (a microhabitat characteristic). These results will help to prioritise and focus control efforts by defining which peridomiciles display a potentially high abundance of Lu. longipalpis.

Prospective comparison of MR enteroclysis with multidetector spiral-CT enteroclysis: interobserver agreement and sensitivity by means of "sign-by-sign" correlation.

Our objective was a prospective comparison of MR enteroclysis (MRE) with multidetector spiral-CT enteroclysis (MSCTE). Fifty patients with various suspected small bowel diseases were investigated by MSCTE and MRE. The MSCTE was performed using slices of 2.5 mm, immediately followed by MRE, obtaining T1- and T2-weighted sequences, including gadolinium-enhanced acquisition with fat saturation. Three radiologists independently evaluated MSCTE and MRE searching for 12 pathological signs. Interobserver agreement was calculated. Sensitivities and specificities resulted from comparison with pathological results ( n=29) and patient's clinical evolution ( n=21). Most pathological signs, such as bowel wall thickening (BWT), bowel wall enhancement (BWE) and lymphadenopathy (ADP), showed better interobserver agreement on MSCTE than on MRE (BWT: 0.65 vs 0.48; BWE: 0.51 vs 0.37; ADP: 0.52 vs 0.15). Sensitivity of MSCTE was higher than that of MRE in detecting BWT (88.9 vs 60%), BWE (78.6 vs 55.5%) and ADP (63.8 vs 14.3%). Wilcoxon signed-rank test revealed significantly better sensitivity of MSCTE than that of MRE for each observer ( p=0.028, p=0.046, p=0.028, respectively). Taking the given study design into account, MSCTE provides better sensitivity in detecting lesions of the small bowel than MRE, with higher interobserver agreement.

What spatial data do we need to develop global mammal conservation strategies?

Spatial data on species distributions are available in two main forms, point locations and distribution maps (polygon ranges and grids). The first are often temporally and spatially biased, and too discontinuous, to be useful (untransformed) in spatial analyses. A variety of modelling approaches are used to transform point locations into maps. We discuss the attributes that point location data and distribution maps must satisfy in order to be useful in conservation planning. We recommend that before point location data are used to produce and/or evaluate distribution models, the dataset should be assessed under a set of criteria, including sample size, age of data, environmental/geographical coverage, independence, accuracy, time relevance and (often forgotten) representation of areas of permanent and natural presence of the species. Distribution maps must satisfy additional attributes if used for conservation analyses and strategies, including minimizing commission and omission errors, credibility of the source/assessors and availability for public screening. We review currently available databases for mammals globally and show that they are highly variable in complying with these attributes. The heterogeneity and weakness of spatial data seriously constrain their utility to global and also sub-global scale conservation analyses.

ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients.

BACKGROUND Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5' CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients. METHODS Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique). RESULTS Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively. CONCLUSION Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient's resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.

Solid pseudopapillary tumor of the pancreas in children: typical radiological findings and pathological correlation.

We report a case series of three children with solid pseudopapillary tumor of the pancreas (SPT) in which a complete radiological work-up, including ultrasound, computed tomography scans, and MRI, has been carried out. The aim of this article is to highlight the characteristic imaging findings of SPT in the pediatric age group and to establish a correlation with typical histopathological findings of the lesion.

Land use improves spatial predictions of mountain plant abundance but not presence-absence

Question Does a land-use variable improve spatial predictions of plant species presence-absence and abundance models at the regional scale in a mountain landscape? Location Western Swiss Alps. Methods Presence-absence generalized linear models (GLM) and abundance ordinal logistic regression models (LRM) were fitted to data on 78 mountain plant species, with topo-climatic and/or land-use variables available at a 25-m resolution. The additional contribution of land use when added to topo-climatic models was evaluated by: (1) assessing the changes in model fit and (2) predictive power, (3) partitioning the deviance respectively explained by the topo-climatic variables and the land-use variable through variation partitioning, and (5) comparing spatial projections. Results Land use significantly improved the fit of presence-absence models but not their predictive power. In contrast, land use significantly improved both the fit and predictive power of abundance models. Variation partitioning also showed that the individual contribution of land use to the deviance explained by presence-absence models was, on average, weak for both GLM and LRM (3.7% and 4.5%, respectively), but changes in spatial projections could nevertheless be important for some species. Conclusions In this mountain area and at our regional scale, land use is important for predicting abundance, but not presence-absence. The importance of adding land-use information depends on the species considered. Even without a marked effect on model fit and predictive performance, adding land use can affect spatial projections of both presence-absence and abundance models.

Modelling world investment markets using threshold conditional correlation models

In this paper we propose a parsimonious regime-switching approach to model the correlations between assets, the threshold conditional correlation (TCC) model. This method allows the dynamics of the correlations to change from one state (or regime) to another as a function of observable transition variables. Our model is similar in spirit to Silvennoinen and Teräsvirta (2009) and Pelletier (2006) but with the appealing feature that it does not suffer from the course of dimensionality. In particular, estimation of the parameters of the TCC involves a simple grid search procedure. In addition, it is easy to guarantee a positive definite correlation matrix because the TCC estimator is given by the sample correlation matrix, which is positive definite by construction. The methodology is illustrated by evaluating the behaviour of international equities, govenrment bonds and major exchange rates, first separately and then jointly. We also test and allow for different parts in the correlation matrix to be governed by different transition variables. For this, we estimate a multi-threshold TCC specification. Further, we evaluate the economic performance of the TCC model against a constant conditional correlation (CCC) estimator using a Diebold-Mariano type test. We conclude that threshold correlation modelling gives rise to a significant reduction in portfolio´s variance.